There is a critical need for technology that will allow the isolation of high quality RNA from histologically preserved clinical samples. The most commonly used fixative, neural buffered formalin severely compromises subsequent isolation of intact nucleic acids. The need for improvement is most acute for techniques that require intact RNA for expression analysis. We proposed a three-track approach. First, we will develop and optimize procedures for the extraction and purification of high quality, reverse- transcription competent RNA from formalin-fixed samples. Second, we will develop new fixation technologies, fully compatible with nucleic acid isolation, by screening existing cross-linking reagents for suitability as fixatives. Finally, we propose synthesizing a novel reversible cross-linking, glutaraldehyde derivative. Ambion, a leading supplier of products for RNA quantitation and analysis, intends to market nucleic acid compatible tissue fixatives and RNA isolation products to the biomedical research community. We believe they will be widely utilized in both basic research and clinical laboratories. PROPOSED COMMERCIAL APPLICATIONS. Improvements to current technologies will allow high quality RNA to be isolated from histologically preserved samples. Ambion will develop and market this methodology in kit form.